Inclusion Criteria:
* Patients must have a recurrent, progressive, or refractory CNS malignancy for which there are not known curative options. Low-grade glioma, craniopharyngioma, and other non-malignant CNS tumors are excluded.
* Tumor must be measureable, defined as a tumor that can be accurately measured in two perpendicular dimensions on MRI.
* Patients with metastatic disease are eligible but must have at least one target lesions which is measurable.
* Patients must have available archival (formalin-fixed paraffin embedded) or fresh tumor tissue for correlative studies.
* Patients must be \>1yrs and \<21 years of age.
* Must have recovered from all surgical interventions prior to the start of the Radiation and Chemotherapy Phases.
* Patients must have recovered from the acute effects of prior therapy.
* There is a maximum of 3 previous myelosuppressive therapy regimens. However, there is no maximum number of therapeutic courses.
* Patients must have received their last dose of known myelosuppressive therapy at least three (3) weeks prior to receipt of SGT-53.
* Patients must have received their last dose of biological agent \>7 days prior to receipt of SGT-53.
* Patients must be far enough from previous irradiation that in the opinion of a radiation oncologist using standard fractionation is deemed to be reasonable from a clinical standard of care perspective.
* Patients who are receiving dexamethasone or other corticosteroids must be on a stable or decreasing dose for at least one (1) week prior to enrollment.
* Patients must have received their last dose of any short acting growth factor at least one week prior to treatment, for long acting or pegylated growth factors, the last dose must be at least two (2) weeks prior to start of treatment.
* Patients with neurologic deficits must have deficits that have been stable in grade for a minimum of one week prior to enrollment.
* Performance status (Karnofsky PS for \>16yrs, or Lansky PS for \<16yrs) assessed within two weeks must be \>50.
* Patients must have normal organ and marrow function.
* All patients of childbearing or child fathering potential must be willing to use an acceptable form of birth control while being treated on this study.
* Female patients must not be pregnant or nursing. Female patients must also have a negative serum pregnancy test at the time of enrollment.
* Patient and/or guardian have the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines.
Exclusion Criteria:
* Patients with any clinically significant unrelated systemic illness (serious infection or significant cardiac, pulmonary, hepatic, or other organ dysfunction) that is likely to interfere with ability to tolerate study therapy or study procedure results.
* Patients with low-grade gliomas, craniopharyngioma, or extracranial tumors with CNS metastases.
* Patients who are receiving any other investigational drug therapy.
* Patients who require therapeutic anti-coagulation.
* Patients who in the opinion of the investigator cannot adhere to protocol requirements.
* Patients with history of clinically significant clot or hemorrhage are eligible but will not receive bevacizumab during chemotherapy regimen.
* Unavailability of the chemotherapy due to insurance coverage or other logistical issues is an ineligibility criterion.
* Patients may not be on immunosuppressive therapy, including corticosteroids (with the exception of physiologic replacement, defined as 0.75mg/m2/day) at time of enrollment. However, patients who require intermittent use of bronchodilators or local steroid injections will not be excluded from the study.
