Inclusion Criteria:

- Histological confirmation of a high-grade malignant glioma is required; histologic
diagnoses include, but are not limited to, anaplastic astrocytoma and glioblastoma
multiforme; patients with DIPG are exempt from histologic verification if they have
typical MRI findings of DIPG (i.e. hypo- or isointense on T1-weighted imaging,
hyperintense on FLAIR or T2-weighted imaging, epicenter in the pons, > 50% of pons
involved) in the face of a typical clinical presentation

- Inoperable tumor or residual disease after resection

- No prior chemotherapy or radiation therapy is permitted

- Able to swallow capsules whole

- Patients should have a Karnofsky/Lansky score of greater than or equal to 60;
patients who require special assistance due to tumor-related paralysis, but who are
out of bed during the day will be considered ambulatory for the purpose of
calculating the performance score; patients must be able to communicate any symptoms

- Absolute neutrophil count >= 1,000/mcL

- Platelets >= 100,000/mcL

- Total bilirubin < 1.5 x upper limit of normal

- AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal

- Creatinine below age-adjusted maximum limits in the table below OR

- 0.8 mg/dl (patients =< 5 years of age)

- 1.0 mg/dl (patients 6 to =< 10 years of age)

- 1.2 mg/dl (patients 11 to =< 15 years of age)

- 1.5 mg/dl (patients > 15 years of age)

- Creatinine clearance >= 60 mL/min/1.73 m^2

- Females only:

- Urine or serum pregnancy test negative

- No overt renal, hepatic, cardiac or pulmonary disease

- Newly diagnosed patients may need to be on steroids due to surgery or control of
neurologic symptoms; patients on steroids postoperatively or for control of
tumor-related edema are eligible, but attempts to keep patients on the lowest dose
necessary to control symptoms should be made

- Appropriate male subjects (i.e. those who have reached puberty and are sexually
active) will be counseled regarding birth control methods; they must agree to use a
latex condom during sexual contact with females of childbearing potential while
participating in the study and for at least 28 days following discontinuation from
the study even if he has undergone a successful vasectomy; appropriate male patients
will be given a reproductive risks handout and counseled by a provider; for sexually
active patients, the counseling session, consent and counseling checklist will be
documented monthly

- Females of childbearing potential (FCBP) must have a negative serum or urine
pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again
within 24 hours prior to starting Course 1 of lenalidomide; further, they must either
commit to continued abstinence from heterosexual intercourse or begin TWO acceptable
methods of birth control: one highly effective method and one additional effective
method AT THE SAME TIME, at least 28 days before starting lenalidomide; FCBP must
also agree to ongoing pregnancy testing. Men must agree to use a latex condom during
sexual contact with a FCBP, even if they have had a successful vasectomy. A FCBP is a
sexually mature woman who: 1) has not undergone a hysterectomy or bilateral
oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive
months (i.e., has had menses at any time in the preceding 24 consecutive months). All
patients must be counseled by a trained counselor every 28 days about pregnancy
precautions and risks of fetal exposure; this protocol defines a female of
childbearing potential as a sexually mature woman who: 1) has not undergone a
hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal
(amenorrhea following cancer therapy does not rule out childbearing potential) for at
least 24 consecutive months (i.e., has had menses at any time in the preceding 24
consecutive months); This protocol defines FCCBP as females who have:

- Achieved menarche and/or breast development in Tanner stage 2 or greater

- Onset of fertility typically occurs within 3-12 months after menarche;
menarche varies considerably from person to person, and thus no age cut off
can be attributed; one of the primary tools used to follow a girl's
progress through puberty is the Tanner staging system, which describes the
pattern of development of the secondary sex characteristics; Tanner stage 2
corresponds to the beginning of breast development, which is the first
visible sign of puberty in girls; breast development is estrogen
stimulated, and since ovulation cannot occur without estrogen, Tanner stage
2 will be a reliable marker for the definition of fertility

- Has not undergone a hysterectomy or bilateral oophorectomy; NOTE: Amenorrhea
following cancer therapy does not rule out childbearing potential

This protocol defines FCNCBP as females:

- Who have not yet experienced menarche or breast development in Tanner stage 2

- Who have undergone a hysterectomy or bilateral oophorectomy.

- All patients or their legal guardians (if the patient is < 18 years old) or
durable power of attorney (DPA) must sign a document of informed consent
indicating their understanding of the investigational nature and the risks of
this study; when appropriate, pediatric patients will be included in all
discussions in order to obtain verbal assent

- Assignment of DPA to a family member or guardian should be offered to all
patients 18 years of age

- Signed informed consent according to institutional guidelines must be obtained

Exclusion Criteria:

- Patients who have had prior chemotherapy for this tumor

- Patients with an HGG that was completed resected with good margins

- Patients with a body surface area (BSA) =< 0.4 m^2 are excluded because the lowest
dose of the medication is 5 mg in capsule form

- Patients with a known coagulation disorder are excluded; patients with a first-degree
relative with a history of venous thrombosis before age 50 yrs or an arterial
thrombosis before age 40 yrs must have the following testing performed prior to
enrollment to exclude a heritable disorder; patients with a suspected disorder will
be excluded due to the potential increased risk of thrombosis

- PT, PTT, thrombin time, fibrinogen

- Antithrombin

- Protein C, protein S

- Factor V Leiden

- Prothrombin G20210A gene analysis

- Fasting serum homocysteine

- Lupus anticoagulant assays

- Anticardiolipin level

- Fasting serum homocysteine

- Anticardiolipin level

- LDL, HDL, triglycerides

- Patients who have had a thromboembolic event that is not line-related are excluded

- Patients with any significant medical illnesses that, in the investigator's opinion,
cannot be adequately controlled with appropriate therapy, would compromise a
patient's ability to tolerate this therapy or result in inability to assess toxicity;
this includes, but is not limited to uncontrolled intercurrent illness including
ongoing or active infection, cardiac disease, renal impairment or psychiatric
illness/social situations that would limit compliance with study requirements

- Patients with a history of toxic epidermal necrolysis (TEN) or Stevens-Johnson
syndrome are excluded as this has occurred in patients receiving lenalidomide

- Patients receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to lenalidomide (i.e. thalidomide)

- Patients with known hypersensitivity to anhydrous lactose, microcrystalline
cellulose, croscarmellose sodium, and magnesium stearate

- Pregnant or breast feeding females

- Known HIV-positive patients on combination antiretroviral therapy are ineligible

- Patients identified as needing spinal radiation at diagnosis (e.g. spinal metastasis
or malignant cells identified on CSF cytology) are excluded