Lenalidomide and Radiation Therapy in High Grade Gliomas or Diffuse Intrinsic Pontine Gliomas

Background: \- Children who are diagnosed with brain tumors known as high grade gliomas or diffuse intrinsic pontine gliomas are generally treated with radiation therapy and chemotherapy. However, these tumors are very difficult to cure, and the tumor frequently begins to grow again even after treatment or surgery. Researchers are interested in determining whether the anticancer drug lenalidomide, which has been used to treat other aggressive types of cancer, is a safe and effective additional treatment for children who are scheduled to receive radiation therapy to treat high grade gliomas or diffuse intrinsic pontine gliomas. Objectives: \- To determine the safety and effectiveness of lenalidomide, in conjunction with radiation therapy, as a treatment for children who have been diagnosed with high grade gliomas or diffuse intrinsic pontine gliomas. Eligibility: \- Children and adolescents up to 21 years of age who have been diagnosed with high grade gliomas or diffuse intrinsic pontine gliomas and have not had radiotherapy or chemotherapy. Design: * Participants will be screened with a medical history, physical examination, blood and urine tests, and imaging studies. * Participants will have two phases of treatment: a lenalidomide plus radiation phase and a lenalidomide-only phase. * During the radiation phase, participants will take lenalidomide daily and have 6 weeks of radiation therapy (five treatments per week). After the radiation therapy, participants will stop taking lenalidomide for 2 weeks before continuing to the next phase. * During the lenalidomide-only phase, participants will take lenalidomide daily for 21 days, followed by 7 days without lenalidomide (28-day cycle of treatment). Participants will have up to 24 cycles of lenalidomide. * Participants will have frequent blood tests during the first cycle of treatment, and will have imaging studies or other tests as required by the study researchers. * Treatment will continue until the disease pr