This protocol is a phase II multi-center randomized controlled trial (RCT) evaluating the efficacy of SBRT in multi-metastatic NSCLC patients who are pan-negative for driver mutations.

Lung cancer is the leading cause of cancer death. Forty percent of patients are diagnosed as metastatic lung cancer, and about 50% of them are pan-negative for driver mutations. The median overall survival(OS) for these patients is 11 months, and maintenance therapy can only prolong 2 months of OS. The NCCN guidelines recommend 4-6 cycles of chemotherapy with or without maintenance chemotherapy.

Published data showed that radiotherapy modulates tumor phenotypes, enhances antigen presentation and tumor immunogenicity. The regression of out-field lesions was termed as "abscopal effect". The combination of radiotherapy with immunotherapeutic agents may promote the host anti-tumor immune response and increase the rate of abscopal effect.Published data showed that abscopal effect appeared in 20%-30% patients with metastatic malignant tumors who were treated with the combination of SBRT and GM-CSF.

The investigators evaluate the efficacy of the combination of SBRT and GM-CSF in the multi-metastatic NSCLC participants who are pan-negative for driver mutations. Patients enrolled will be randomized into two groups. The control group will receive the standard regimen as NCCN recommends. The experimental group will receive both the standard chemotherapy and the extra SBRT to primary lesions or metastatic lesions combined with GM-CSF. The investigators compare progress free survival(PFS) of the two groups.

Inclusion Criteria:

• Histologically proven non-small-cell lung cancer.
• Stage IV according to UICC stage system(version 7,2009).The number of metastatic lesions>5
• Pan-negative for driver mutations including EGFR ALK ROS1 c-MET
• At least Three evaluable lesions among which at least two must be suitable for SBRT.
• ECOG performance status 0-2.
• Expected lifespan ≥3 months.
• No brain metastasis in MRI.
• No liver metastasis in abdominal CT or MRI.
• No malignant pleural effusion or pericardial effusion from chest CT and/or pathology.
• Stable lab values: Hematological:

Absolute neutrophil count (ANC) ≥1.5×109/L, Platelets ≥100×109/L, Hemoglobin ≥9 g/dL Renal: Creatinine OR Measured or calculated creatinine clearance (CrCl) (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) ≤1.5× the upper limit of normal (ULN) OR ≥60 mL/min for patient with creatinine levels >1.5× institutional ULN Hepatic: Total bilirubin ≤1.5×ULN OR Direct bilirubin ≤ULN for patients with total bilirubin levels >1.5×ULN, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN OR ≤5×ULN for patients with liver metastases ,globulin≥20 g/L, albumin≥30 g/L.

- Able to understand and give written informed consent and comply with study procedures.

Exclusion Criteria:

• Any unstable systemic disease, including active infection, uncontrolled high blood pressure, unstable angina, newly observed angina pectoris within the past 3 months, congestive heart failure (New York heart association (NYHA) class II or higher), myocardial infarction onset six months before included into the group, and severe arrhythmia, liver, kidney, or metabolic disease in need of drug therapy.
• Previously diagnosed with immunodeficiency disease.
• Human immunodeficiency virus (HIV) infection.
• Women in pregnancy or lactation .
• Patients with mental illness, considered as "can't fully understand the issues of this research".
• other Cancer history.
• Histologically confirmed small cell carcinoma or other non NSCLC compositions in the cancer tissue.
• Brain metastasis or liver metastasis or malignant pleural effusion or pericardial effusion.
• Allergy of rhGM-CSF and its accessories.
• Contraindications to GM-CSF treatment.